The purpose of the project is to undertake a systematic study of the interaction of follitropin (FSH) with specific receptors in rat testes. Highly purified human or animal FSH, radioiodinated under conditions which permit retention of biological activity, will be utilized as the radioligand in these studies. Tubules from testes of mature and immature, normal and hypophysectomized male rats will be utilized as the receptor model. A comparison will be made of the properties of FSH receptors present in highly purified tubule plasma membranes, with putative solubilized FSH receptors. Solubilization of the receptor will be attempted through use of non-ionic detergents, chaotropic agents, organic solvents and other means as may prove appropriate. These studies will require development of a quantitative assay for the solubilized receptor. Chemical purification of the receptor will be pursued by a variety of methods, but it is hoped that affinity chromatography will allow a rapid advance in this area. The properties of the receptor will be probed through use of chemical and enzymatic modification. The relationship between hormone binding to activation of adenylate and other cyclase systems will be studied. An investigation of the interaction of FSH and/or its asialo derivative with receptors in liver and kidney will be undertaken, as these may be important factors related to the metabolism of the FSH. We will attempt to define the structural requirements of the hormone for binding to the receptor and of the receptor for interaction with FSH. The nature and properties of testicular "factors" which appear to interfere (inhibit) with the uptake of FSH by receptors will be intensively studied in order to ascertain their possible physiologic relevance and evaluate their potential application in contraception. Based on our experience in the rat system, similar studies of a comparative nature will be performed with testes from other species, as may prove appropriate.